The general ofjective of this project is to gain a better understanding of how the structure and mechanical propertied of lung tiddue, airways, and pulmonary blood vessels change under physical stress such as hypertension, or disease such as diabetes, and how do the changes affect the pressure and flow in the Lung. The Specific Aims are: (1) To determine the zero-stress state of al generations of pulmonary blood vessels and airways, and their changes due to tissue remodeling in hypertension and other disease, and to correlate them with other markers of remodeling such as hypertrophy, cell proliferation, DNA content, and radioactive thymidine incorporation. (2) To determine the remodeling of the mechanical properties of different layers of pulmonary blood vessels and airways and pulmonary capillaries. (3) To distill the infformation obtained into constitutive equations describing the mechanical properties of the tissues, with coefficients depending on species, location, and disease states. (4) To use the remodeling data and constitutive equations to predict the pressure and flow distribution in the lung in pulmonary hypertension and diabetes, and to validate the theory with experiments. The point of departure of this study is our new discovery that at the zero-stress state the pulmonary artery is not an unloaded tube. If we take an artery, cut a short segment out, then cut the ring radially, it will spring open into a sector. An opening angle of the sector is defined as the angle between two radii joining the midpoint of the inner wall to the tips of the inner wall. This angle varies with the location on the vascular tree. In some parts it can be greater than 180 degrees. In the main pulmonary artery of the rat, it is often 360 degrees or larger; and it changes with the onset of hypertension and diseases. This opening angle reveals the zero-stress state of the vessel at which the different layers of the vessel (ensothelium, collagen and elastin layers, smooth muscle cells, adventitia) are put together without being deformed by residual stress. Any stress calculation must be based on the zero- stress state. We define strains from the zero-stress state, and use load-deformation relationship to determine the constitutive equations. With information on the remodeling of structure, materials, cellular growth, and mechanical properties, a theory to predict the changes in pressure-flow relationship will be formulated and validated with experiments.